Chlamydial species cause a wide range of diseases in both animals and humans. Of particular concern is C. trachomatis, an obligatory intracellular bacterium, which infects and multiplies in epithelial cells. It is the most frequent cause of sexually transmitted disease (STD) in developed countries and it is the most common cause of ocular disease in developing countries (Schachter, Moncada et al. 1988). There is an estimated 92 million individuals who carry the infection globally (WHO, 1999).
The duration of untreated Chlamydia STD is prolonged, and complete clearance is often not reached within the first 12 months. The protective immunity induced during the infection is thought to be serovariant-specific and short-lived, thus allowing frequent re-infections (Katz, Batteiger et al. 1987). These circumstances, the prolonged course of infection and the possible re-infections may lead to the development of serious sequelae, including pelvic inflammatory disease, infertility and ectopic pregnancies (Brunham 1999).
The infection is effectively controlled by antibiotic therapy; however the high prevalence of asymptomatic cases suggests that sustainable Chlamydia control can only be envisaged if an effective Chlamydia vaccine is developed. While much effort has been devoted to a vaccine against Chlamydia infections over the last few decades, so far no vaccine has been developed.
This makes the development of a vaccine against Chlamydia an urgent matter. Many attempts to define protective chlamydial substances have been made, however, the demonstration of a specific long-term protective immune response has not yet been achieved. Over the last several decades much effort has been devoted into developing a vaccine against Chlamydia infections however, so far no vaccine has been developed. Some of the first efforts were focused on controlling trachoma, and whole viable or inactivated organisms were used as the antigen to immunize humans and monkeys (Wang, Grayston et al. 1967; Grayston and Wang 1978). Children vaccinated with an inactivated whole-cell vaccine initially resulted in protection but the protection was serovar specific and short-lived (Grayston and Wang 1978). Furthermore, reinfection of partially protected individuals resulted in clinical disease that was more sever than the disease occurring in non-vaccinated controls (Grayston and Wang 1978). The fact that the initial trials with inactivated whole organisms resulted in some cases of what appeared to be a hypersensitivity reaction prompted attempts to develop subunit vaccines.
C. trachomatis holds, as well as secretes, several proteins of potential relevance for the generation of a chlamydia vaccine. For a number of years, the search for candidate molecules has primarily focused on proteins associated with the surface of the infectious form the Elementary Body (EB). Despite the characterization of a large number of such proteins only a few of these have been demonstrated to elicit partial protection as subunit vaccines in animal models. The first immunogenic molecule described was the major outer membrane protein (MOMP), and this molecule has therefore been studied in great detail as a candidate vaccine. However, many attempts to immunize different animals with MOMP extracted from C. trachomatis or recombinant preparations gave variable results (Su, Parnell et al. 1995; Pal, Barnhart et al. 1999; Zhang, Yang et al. 1999; Pal, Theodor et al. 2001; Shaw, Grund et al. 2002). The reason for the relative ineffectiveness of MOMP as a vaccine is not known, but may result from inadequate adjuvants or delivery systems or from use of MOMP immunogens that do not mimic the native structure of the protein (Pal, Theodor et al. 2001)
More recently, several other immunogenic molecules have been identified (Hassell, Reynolds et al. 1993; Kubo and Stephens 2000; LaVerda, Albanese et al. 2000; Fling, Sutherland et al. 2001; Goodall, Yeo et al. 2001; Starnbach, Loomis et al. 2003). Immunity to C. trachomatis is characterized by some basic features; specifically sensitized T lymphocytes mediates protection (Su and Caldwell 1995; Morrison, Su et al. 2000; Morrison and Caldwell 2002), and the most important mediator molecule seems to be interferon gamma (IFNγ) (Morrison and Caldwell 2002). Additionally antibodies of the IgG, IgM, and IgA isotypes may also play a role (Cotter, Meng et al. 1995). In 1995 Tripples et al. (Tipples and McClarty 1995) isolated the gene for the CTP synthetase and Gu et al. (Gu, Wenman et al. 1995) cloned the region surrounding the gene for the alpha subunit of RNA polymerase. This region also contains genes for the proteins SecY, S13, S11, and L17, which are equivalent to Escherichia coli and Bacillus subtilis proteins. In 1997, the gene for elongation factor Ts was isolated (Zhang, Tao et al. 1997).
In 1998 Stevens et al published the complete genome sequence of C. trachomatis and predicted the presence of approximately 875 open reading frames. Among others, nucleotide sequences comprising CT442, CT460, CT509 CT579, CT587, CT713, CT812, or CT681 (MOMP) are described, and putative protein sequences for the above sequences are suggested. However importantly, this sequence information cannot be used to predict if the DNA is transcribed and translated into proteins in vivo.
More importantly, it is not possible on the basis of the sequences, to predict whether a given sequence will encode an immunogenic or an inactive protein. WO9928475 describes the complete genome sequence of C. trachomatis but has no evidence in support of any immunogenic effect whatsoever. Correspondingly WO9927105 describes the complete genome sequence of C. pneumoniae. 
The only way to determine if a protein is recognized by the immune system during or after an infection with C. trachomatis is to produce the given protein and test it in an appropriate assay as described herein and possibly determine the fragment or epitope that has an immunogenic effect.